血脂管理(2010年)

RobertH.Eckel,M.D.ProfessorofMedicineDivisionofEndocrinology,MetabolismandDiabetesDivisionofCardiologyProfessorofPhysiologyandBiophysicsCharlesA.BoettcherIIChairinAtherosclerosisUniversityofColoradoDenverSchoolofMedicineDirectorLipidClinic,UniversityHospital“Lipidology(PreATP-IV):EverythingICanDiscussonWhatYouShouldKnow”HowtoPreventaHeartAttackJune12,2010TheLipidPatientFiveGroups•LDLcholesterol•TG(HDLcholesterol•LDLcholesterol+TG•HDLcholesterol•Lipoprotein(a)AssessingAcquiredCausesofDyslipidemia•Lifestyle–Diet,inactivity,alcohol,tobacco•Medications–Steroids,diuretics,-blockers,PIs,cis-RA•Insulinresistance•Thyroiddisease•Liverdisease•Kidneydisease–Proteinuria–GFRRevisedNCEPATPIIILDL-CGoalsCirculation110:227,2004ModeratelyHigh190*0–1RF’s160*2+RF(10-20%/10yrs)100*CHDorRiskEquivalent(20%/10yrs)High(VeryHigh)ConsiderDrugRxCHDRiskCategoryLDL-CGoal100(70)1301602+RF(10%/10yrs)ModerateLow130130**Considerdrugoptionsifbelowgoal,butabovegoalfornexthigherrisklevelRevisedNCEPATPIIINon-HDLGoalsCirculation110:227,2004ModeratelyHigh190*0–1RF’s190*2+RF(10-20%/10yrs)130*CHDorRiskEquivalent(20%/10yrs)High(VeryHigh)ConsiderDrugRxCHDRiskCategoryNon-HDL-CGoal130(100)1601902+RF(10%/10yrs)ModerateLow190160**Considerdrugoptionsifbelowgoal,butabovegoalfornexthigherrisklevelNHLBIClinicalGuidelinesforCVDRiskReduction:OrganizationalStructureNHLBIDirectorDARDDirectorDARDProjectTeamSAICSupportContractGuidelineLeadershipGroupClinicalGuidelinesExecutiveCommitteeExpertPanelfortheIntegratedCVDGuidelineDevelopmentExpertPanelforCholesterolUpdatesExpertPanelforHypertensionUpdatesExpertPanelforObesityUpdatesRiskAssessmentLifestyle/Nutrition/PAImplementation/System/IT/InformaticsCross-CuttingWorkgroupsMajorLipids,ApolipoproteinsandCVDRisk:TheEmergingRiskFactorsCollaboration•302,430peoplewithoutCVDfrom68long-termprospectivestudies–MostlyEuropeandNorthAmerica•2.79millionperson-yearsoffollow-up–8857non-fatalMIs–3928CHDdeaths–2534ischemicstrokes–513hemorrhagicstrokes–2536unclassifiedstrokesERFCollaboration,JAMA302:1993,2009CHDRisk:Non-HDLvs.HDLCholesterolERFCollaboration,JAMA302:1993,2009(n=302,430)ApolipoproteinBOneapoBmolecule/particleAssessespotentiallyatherogenicparticlenumberHelpstodistinguishriskofCHDinpatientswithhypertriglyceridemiaHighlycorrelatedwithnon-HDLcholesterol•0.95whenTG300mg/dl•0.80whenTGhigherApoBMayPredictVascularEventsBetterthanLDLCholesterol•Observationalstudies–QuebecCardiovascularStudy–LIPID(placebo)–AMORIS•Interventionalstudies–AFCAPS/TexCAPS(lovastatin)–LIPID(pravastatin)–IDEAL(simvastatin,atorvastatin)–TNT(atorvastatin)CHDRiskBasedonLipidsandApolipoproteinsERFCollaboration,JAMA302:1993,2009(n=91,307)TherealvalueofapoBisinpatientswithoutincreasesinLDLcholesterol,inpatientswithhypertriglyceridemia0.00.51.01.52.02.53.050100150200250300350400MenWomenRRTG(mg/dL)CastelliWP.CanJCardiol.4:5A,1988ImpactofTGLevelsonRelativeRiskofCHD:FraminghamHeartStudyHypertriglyceridemia(1mM)andCHD:AMeta-Analysis(21studies)MEN(65,863):1.30(1.25-1.35)WOMEN(11,089):1.69(1.45-1.97)AdjustedforHDLcholesterol(9studies):MEN(29,105):1.17(1.10-1.26)WOMEN(6,345):1.37(1.13-1.66)Abdul-MaksoudMandHokansonJ.E.,JVascMed,2001RelativeRiskSarwar,N.etal.Circulation2007;115:450-458RiskofCHDintheTopvs.BottomTertileofUsualLog-TGbyStudyCharacteristicsSarwarNetal,Circulation115:450,2007ThompsonAandDaneshJ,JournalofInternalMedicine,259:481,2006ApoBandCHDRisk:MetaAnalysisCHDandIschemicCVARisk:EmergingRiskFactorsCollaborationMeta-Analysis(n=302,430people)ERFCollaboration,JAMA302:1993,2009CHDCVANormalIIAIIBIVNlTGTGHDLLamarcheBetal,AmJCard75:1189,19951.0(0.001)2.81.71.0(0.005)2.7(0.001)3.1(0.01)2.1OROddsareadjustedforage,smoking,alcohol,bloodpressure,gender,andmedicationsHyperapoBOddsRatiosfortheDevelopmentofCHD:LipidandLipoproteinPhenotypesManagementofTriglyceridesGoal:IsitTG?No,it’snon-HDLcholesterol!Thenisn’titTG150mg/dl?OrshoulditbeapoB?CorrelationsBetweenApoB,Cholesterol,LDLCholesterolandNon-HDLCholesterolSnidermanASetal,AmJ.Card91:1173,2003ACC/ADALipidGoalsLDL-CNon-HDL-CApoBCHDorDM+1RiskFactor70mg/dl100mg/dl80mg/dl≥2RiskFactorsorDM100mg/dl130mg/dl90mg/dlBrunzellJDetal,JACC51:1512,2008LDL-C(mg/dL)353025201510500255075100125150175200EventRate(%)Clinicalstatintrialdata4SP4STxLIPIDPHPSPLIPIDTxHPSTxCAREPTNT10mgTNT80mgLDL-CReductioninStatinTrialsCharlandSL,etal.Circulation2005;112:II-816iEmaxmodel,r2=0.82,p=0.01CARETxStatins:TheDownSide•AbnormalASTandALT–3XULN:~1.3%–3XULN:1.0%•Doserelated•Myopathy:Anydiseaseofmuscles–Myalgias:paininamuscleofgroupofmuscles•~10%–Myositis:musclesymptomswithCK•~2.5%–Rhabdomyolysis:50foldinCK+renalimpairment•0.1%BruckertEetal,CardiovDrugs19:403,2005BrownWV,CurrOpinLipid19:558,2008OnuskoE,JFamPract57:449,2008WhattheClinicianNeedstoConsider•Hypothyroidism•Otherdrugs–Fibrates,azoleanti-fungals,cyclosporine,macrolides,diltiazem,HIVproteaseinhibitors•Geneticdifferencesindrug-metabolizingenzymes,e.g.OATP1B1–SLCO1B1,CYP2D2,3A4•Neuromusculardiseases–Mitochondrialmyopathy,McArdlesdisease,myotonicdystroph